Reproducibility and Characterization of Head Kinematics During a Large Animal Acceleration Model of Traumatic Brain Injury.

Andrew R Mayer,Meghan S Vermillion,Victoria E Johnson,David D Stephenson,Sharvani Pabbathi Reddy,Rachel Kinsler,Douglas H Smith,Timothy B Meier,Cidney R Robertson-Benta,Rebecca J Dodd,Declan A Patton,Carissa J Mehos,Josef M Ling,Julie G Rannou-Latella,Andrew B Dodd,Andrew P Gigliotti,D Kacy Cullen

doi:10.3389/fneur.2021.658461

Abstract

Acceleration parameters have been utilized for the last six decades to investigate pathology in both human and animal models of traumatic brain injury (TBI), design safety equipment, and develop injury thresholds. Previous large animal models have quantified acceleration from impulsive loading forces (i.e., machine/object kinematics) rather than directly measuring head kinematics. No study has evaluated the reproducibility of head kinematics in large animal models. Nine (five males) sexually mature Yucatan swine were exposed to head rotation at a targeted peak angular velocity of 250 rad/s in the coronal plane. The results indicated that the measured peak angular velocity of the skull was 51% of the impulsive load, was experienced over 91% longer duration, and was multi- rather than uni-planar. These findings were replicated in a second experiment with a smaller cohort (N = 4). The reproducibility of skull kinematics data was mostly within acceptable ranges based on published industry standards, although the coefficients of variation (8.9% for peak angular velocity or 12.3% for duration) were higher than the impulsive loading parameters produced by the machine (1.1 vs. 2.5%, respectively). Immunohistochemical markers of diffuse axonal injury and blood–brain barrier breach were not associated with variation in either skull or machine kinematics, suggesting that the observed levels of variance in skull kinematics may not be biologically meaningful with the current sample sizes. The findings highlight the reproducibility of a large animal acceleration model of TBI and the importance of direct measurements of skull kinematics to determine the magnitude of angular velocity, refine injury criteria, and determine critical thresholds.

Highlights

Heterogeneous in nature, most human traumatic brain injuries (TBI) are caused by the transmission of energy from an external force to the head that subsequently results in rapid acceleration/deceleration of the brain with or without deformation of the skull [1]
Head and machine kinematic data were successfully collected in nine of 10 attempts (178.3 ± 5.5 days old; 26.4 ± 1.4 kg; four females) during experiment 1, with the mounting plate screws failing during one procedure
The results indicate comparable data recorded from both sensors for the coronal axis

Summary

Introduction

Most human traumatic brain injuries (TBI) are caused by the transmission of energy from an external force to the head that subsequently results in rapid acceleration/deceleration of the brain with or without deformation of the skull [1]. Head kinematics have been used to predict TBI pathology in both human and animal models, design safety equipment, and assess the risk of brain injury [2,3,4]. To our knowledge, there have only been a handful of large animal studies that have used sensors [5,6,7,8,9] and/or high-speed cameras [see Table 1; [8, 10, 11]] to directly measure the magnitude of head kinematics during acceleration models of injury. Rodent acceleration models have been proposed [70], examination of the effects of linear and rotational accelerative forces is more practical in gyrencephalic animal species with a larger brain mass [11, 71]

Methods

Results

Conclusion